Post on 01-Apr-2015
Leicester Warwick Medical School
Haemostasis Thrombosis and Embolism
Dr. Kevin Westkpw2@le.ac.uk
Department of Pathology
Why don’t you bleed to death from a minor injury?
Objectives 1
• Haemostasis
Objectives 2
• Thrombosis– definition– predisposing factors– effects – outcomes – common clinical examples
Objectives 3
• Embolism– definition– thromboembolism– other types of embolism– pathogenesis of DVT and pulmonary embolism– pathophysiology of pulmonary embolism– prevention and treatment of thrombo-embolic
disease
Haemostasis
Successful haemostasis depends on
• vessel wall
• platelets
• coagulation system
• fibrinolytic system
Blood Vessels
• constrict to limit blood loss
• arteries, veins, capillaries
• mechanism not fully understood
Platelets
• adhere to damaged vessel wall
• adhere to each other
• form a platelet plug
• platelet release reaction
Platelet Release Reaction
• ATP ADP
• ADP, thromboxane A2 cause platelet aggregation
• 5HT, platelet factor 3 also released
• PF3 important in coagulation
• Platelets coalesce after aggregation
Coagulation
• Cascade
• Series of inactive components converted to active components
• Prothrombin Thrombin
Fibrinogen Fibrin
Coagulation
• 1 ml of blood can generate enough thrombin to convert all the fibrinogen in the body to fibrin
• Tight regulation therefore required
• Balance of procoagulant and anticoagulant forces
Control of Coagulation
• Thrombin destroys factors V and VIII• Thrombin inhibitors
– anti-thrombin III*– alpha 1 anti-trypsin– alpha 2 macroglobulin– protein C and S*
* inherited deficiency may thrombosis
Fibrinolysis
• Breakdown of fibrin• Plasminogen Plasmin
Plasminogen activators
• Fibrinolytic therapy widely used– streptokinase– tPA
Endothelium
• Anti-thrombotic– plasminogen activators– prostacyclin– nitric oxide– thrombomodulin
Thrombosis
• Definition
Thrombosis is the formation of a solid mass of blood within the circulatory system
Why does thrombosis occur?
• Abnormalities of the vessel wall– atheroma– direct injury– inflammation
Why does thrombosis occur?
• Abnormalities of blood flow– stagnation– turbulence
• Abnormalities of blood components– smokers– post-partum– post-op
Appearances of thrombi
• Arterial– pale– granular– lines of Zahn– lower cell content
Appearances of thrombi
Appearances of thrombi
• Venous– soft– gelatinous– deep red– higher cell content
Outcomes of thrombosis
• Lysis– complete dissolution of thrombus– fibrinolytic system active– bloodflow re-established– most likely when thrombi are small
Outcomes of thrombosis
• Propagation– progressive spread
of thrombosis– distally in arteries– proximally in veins
Outcomes of thrombosis
• Organisation– reparative process– ingrowth of
fibroblasts and capillaries (similar to granulation tissue)
– lumen remains obstructed
Outcomes of thrombosis
• Recanalisation– bloodflow re-
established but usually incompletely
– one or more channels formed through organising thrombus
Outcomes of thrombosis
• Embolism– part of thrombus breaks off– travels through bloodstream– lodges at distant site
Effects of thrombosis
• Arterial– ischaemia– infarction– depends on site and
collateral circulation
• Venous– congestion– oedema– ischaemia– infarction
Coronary artery thrombosis
Coronary artery thrombosis
Rudolf Virchow
• b. Pomerania 1821• graduated in
medicine 1843• presented work on
thrombosis 1845 but could not get it published
• founded own journal
Rudolf Virchow
• 1848 studied typhus epidemic in Prussia
• Attributed typhus to poor social conditions which upset the government
• Became a political activist and was sacked in 1849 after building barricades in Berlin uprising
Rudolf Virchow
• Appointed Professor of Pathology in Wurzburg
• Described leukaemia, pulmonary embolism and much more
• 1856 appointed Professor of Pathology in Berlin despite government opposition
Rudolf Virchow
• 1858 published ‘Cellular Pathology’ one of the most influential medical books ever written
• 1880-93 Member of Reichstag
• Died aged 81 after fracturing his hip jumping from a moving tram
Embolism
• Definition
Embolism is the blockage of a blood vessel by solid, liquid or gas at a site distant from its origin.
>90% of emboli are thrombo-emboli
Embolism
• Other types– air– amniotic fluid– nitrogen– medical equipment– tumour cells
Thrombo-emboli
• from systemic veins pass to the lungs = pulmonary emboli
• from the heart pass via the aorta to renal, mesenteric, and other femoral arteries
• from atheromatous carotid arteries pass to the brain
• from atheromatous abdominal aorta pass to arteries of the legs
Deep vein thrombosis
• predisposing factors– immobility/bed rest– post-operative– pregnancy and post-
partum– oral contraceptives– severe burns – cardiac failure– disseminated cancer
Can DVT be prevented?
• high risk patients must be identified and offered prophylaxis– heparin sub-cutaneously– leg compression during surgery
Can DVT be treated?
• intravenous heparin
• oral warfarin
Pulmonary embolism - effects
• massive PE >60% reduction in bloodflow rapidly fatal
• major PE - medium sized vessels blocked. Patients short of breath +/- cough and blood stained sputum
• minor PE - small peripheral pulmonary arteries blocked. Asymptomatic or minor shortness of breath
• recurrent minor PEs lead to pulmonary hypertension
Pulmonary embolism